Structural basis of BMP-2 and BMP-7 interactions with antagonists Gremlin-1 and Noggin in Glioblastoma tumors.
J Comput Chem
; 41(30): 2544-2561, 2020 11 15.
Article
en En
| MEDLINE
| ID: mdl-32935366
ABSTRACT
In Glioblastoma (GBM) brain tumors, both Gremlin-1 and Noggin are reported to bind to BMP and inhibit BMP-signaling, thereby allowing the cell to maintain tumorous morphology. Enlisting the interfacial residues important for protein-protein complex formation between BMPs (BMP-2 and BMP-7) and antagonists (Gremlin-1 and Noggin), we analyzed the structural basis of their interactions. We found possible key mutations that destabilize these complexes, which may prevent GBM development. It was also observed that when the interfacial residues were either mutated to histidine or tryptophan, it led to higher destabilization energy values. Besides, our study of the Noggin interactive model of BMP-2 suggested preferential binding at binding site II over binding site I. In the case of Gremlin-1 and BMPs, our research, along with few previous studies, indicates a close-ended cis-trans interactive model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
/
Glioblastoma
/
Péptidos y Proteínas de Señalización Intercelular
/
Proteína Morfogenética Ósea 2
/
Proteína Morfogenética Ósea 7
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Comput Chem
Asunto de la revista:
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
India